Diethyl hydrogen phosphite preparation

Isopropanol has been used in the above experiment because it gives a greater yield of the phosphite than ethanol gives of diethyl hydrogen phosphite. The latter, b.p. 74 /i4 mm., can be prepared by replacing the isopropanol in the above experiment by 29 ml. (23 g.) of ethanol. 

An interesting application of this method is the preparation of (0,P)- and N,P)-acetals, not otherwise an easy process. Treatment of an aldehyde with diethyl hydrogen phosphite in the presence of TiCU affords the (a-hydroxy) phosphonate in good yield (Eq. 235) [539,540]. Alternatively, the methoxy group of an (N,0)-acetal was replaced with a phosphonate group via the reaction of triethyl phosphite and TiCU (Eq. 236) [541], In the latter reaction the resultant phosphonate was subsequently used as an olefination reagent. 

These compounds can be prepared by the action of bromine on a trialkyl phosphite,2 but a more satisfactory method recently worked out by Goldwhite and Saunders3 consists in treating the dialkyl hydrogen phosphite with iV-bromosuccinimide. In this way dimethyl, diethyl w-propyl and isopropyl phosphoro-bromidates have been obtained as pure liquids by distillation at very low temperature. When kept at ordinary temperatures, they gradually decompose with the evolution of the corresponding alkyl bromide. 

Although the action of POClaF on an alcohol cannot compete with the hydrogen phosphite method for large-scale work, the (vmer was found extremely valuable for exploratory purposes. In particular, it was found possible to prepare diaryl phosphoro-fluoridates (e.g. (C,H50)aPOF) and diethyl phosphorofluorido-dithiolate (diethyl dithiofluorophosphonate, (CaH5S)aPOF) by the action of phosphorus oxydichlorofluoride on the appropriate phenol or mercaptan. 

Schrader prepared the ester (38) in 60% yield by reaction of sodium p-nitrophenate with diethyl chlorophosphate, using xylene as solvent for the reaction. He made it, but in lower yields, from p-nitrophenol and diethyl chlorophosphate, using, respectively, pyridine and sodium cyanide as acceptors for hydrogen chloride. Schrader also prepared it in 96% yield by nitrating diethyl phenyl phosphate at 0° C. or below. Under the conditions he used, Schrader claims that the nitro group is directed to the para position. No yield is given for the diethyl phenyl phosphate, which he presumably made from sodium phenate and diethyl chlorophosphate. Diethyl chlorophosphate may be prepared in high yield (30) from diethyl phosphite and chlorine. 

Many communications have concentrated on specific amino phosphonic acids or derivative types. Thus, esters of phosphonoaminoacetic add were obtained by the reactions between trialkyl (ethyl) phosphite and (218) and which are thought to proceed via the phosphorane (219). A sequence has been presented for the preparation of the mono- and di-benzyl esters of N-chz protected (a-aminoben-zyl)phosphonic acid. A synthesis of (aminomethylene)bisphosphonic acid from dibenzylamine, dibenzyl hydrogenphosphonate and triethyl orthoformate has been noted and the asymmetric hydrogenation of (220) in the presence of chiral phosphine catalysts yields samples of (221) with e.e.s of 63-96%. The pyrrolidine-based compound (222) has been prepared from methyl S)-N-methoxycarbonyl-4-oxo-2-pyrrolidinecarboxylate and iV-coupled 4-amino-butanal diethyl acetals were the starting materials in syntheses of the pyrrolidine-2-phosphonic add derivatives (223) in which Z represents the iV-protected amino add or peptide moiety. ... 

A synthesis of racemic fmoc-protected 4-phosphonomethylphenylalanine starts with the Arbuzov preparation of (257) (R = Me or Bu ) standard modifications to the aryl methyl group lead to the desired (258). Two procedures have been adopted for the preparation of the N-ivaoc or iV-boc derivatives of the difluoro derivative (259). In the first, triethyl phosphite and 4-(bromomethyl)benzoyl bromide and treatment of the resultant aroyl phosphonate with the DAST reagent yields (262) this reacts with the carbanion from (263) to give (264) hydrogenation of which (with PdCla) affords (260), then converted into its N-fmoc derivative and de-esterified with MeaSil. In the second procedure, triethyl phosphite and 4-iodobenzoyl chloride, followed by DAST reagent, yielded diethyl [difluoro(4-iodophenyl)methyl]phosphonate which was caused to react... 

One laboratory method of preparation of AEP is by the catalytic reduction of diethyl cyanometh-ylphosphonate with hydrogen and Raney nickel the starting material can be obtained by heating triethyl phosphite with chloroacetonitrile at 140-150°C. 

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